The present invention is generally in the area of methods and devices to obtain vascular tissue grafts and more specifically in the area of methods and devices to obtain grafts, preferably autologous grafts, prepared from living vascular tissue.
Vascular grafts are commonly used by surgeons to bypass obstructions to blood flow caused by the presence of atherosclerotic plaques. Vascular grafts also are used in other applications such as providing arterial-venous shunts in dialysis patients, vascular repair or replacement and treating aneurysms. Grafts for bypass are often, but not exclusively, used in the coronary arteries, the arteries that supply blood to the heart. The materials used to construct a vascular graft usually are either synthetic or of biological origin, but combinations of synthetic and biological materials are under development. The most widely used biological vascular grafts are autologous saphenous vein or mammary artery. Some common synthetic grafts are made of polytetrafluoroethylene (PTFE) (e.g., GORTEX(trademark)) or polyester (e.g., DACRON(trademark)). Autologous grafts have generally been used more successfully than synthetic grafts. Autologous grafts remain patent (functional) much longer than synthetic grafts, and saphenous veins often fail in less than five years. The short lifetime of synthetic grafts is especially evident with small diameter (less than 7 mm diameter) grafts, as most small diameter synthetic grafts occlude within one to two years or less.
Small diameter vascular grafts are particularly used in coronary artery bypass surgery. Internal mammary artery (IMA) is the autologous graft of choice, because it typically has a longer life than venous grafts (95% patent at 5 years versus 85% patent at 2 years). Mammary arterial tissue, however, is difficult to harvest, typically is not available in lengths sufficient for multiple bypasses, and its removal can result in problems such as problematic wound healing. Moreover, obtaining sufficient venous tissue for repairing an occluded artery can be problematic in patients with venous conditions such as varicose veins and especially in second or third surgeries in the same patient. Recent literature also suggests that IMA used in bypass procedures either fails soon after transplantation or remains patent indefinitely. See, e.g., Bergsma, et al., Circulation 97(24):2402-05 (1998); Cooley, Circulation 97(24):2384-85 (1998). Other arteries such as the gastroepipolic, gastric, radial, and splenic also are used in coronary bypass procedures. Moreover, the recent American Heart Association/American College of Cardiology consensus document (Eagle, K.A., et al. xe2x80x9cACC/AHA Guidelines for coronary artery bypass graft surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelinesxe2x80x9d, Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery, American College of Cardiology/American Heart Association, J. Am. Coll. Cardiol., 34(4):1262-347 (1999)) strongly recommends a move to total arterial revascularization.
In some cases, autologous or homologous saphenous vein preserved by freezing or other processes is used.
With people living longer, multiple surgeries are more common. At the same time, open-heart surgery is becoming routine, aided by the development of new, minimally invasive and xe2x80x9coff-pumpxe2x80x9d procedures that have dramatically simplified the surgery and reduced the recovery time.
Development of a longer lasting small-diameter vascular graft is the subject of much academic and industrial research. One current approach is to combine cell culture and biomaterials technologies to make a living, xe2x80x9ctissue engineeredxe2x80x9d graft. This effort, however, is hindered by the requirements of a successful graft: It should be self-repairing, non-immunogenic, non-toxic, and non-thrombogenic. The graft also should have a compliance comparable to the artery being repaired, be easily sutured by a surgeon, and not require any special techniques or handling procedures. Grafts having these characteristics are difficult to achieve. Despite the substantial effort to date and the potential for significant financial reward, academic and industrial investigators have failed to produce graft materials that have demonstrated efficacy in human testing.
Efforts to avoid or minimize the need for vascular grafts for repair of otherwise healthy vascular tissue have been described. For example, Ruiz-Razura et al., J. Reconstructive Microsurgery, 10(6):367-373 (1994) and Stark et al., Plastic and Reconstructive Surgery, 80(4):570-578 (1987) disclose the use of a round microvascular tissue expander for acute arterial elongation to examine the effects on the tissue of such acute hyperextension. The expander is a silicone balloon that is placed under the vessel to be elongated. The balloon is filled with saline over a very short period, causing acute stretching and elongation of the vessel. The method is purported to be effective for closure of arterial defects up to 30 mm without the need for a vein graft. These techniques are appropriate for trauma, but are not used for restoring blood flow in vessels that are occluded, for example by disease, which are treated by surgically bypassing the obstruction with a graft. The disclosed methods and devices fail to provide an autologous graft or versatile substitute. Moreover, the acute stretching may damage the vessel.
It is therefore an object of the present invention to provide devices and methods for creating natural blood vessel suitable for grafting.
It is another object of the present invention to provide devices and methods for making an autologous blood vessel graft.
It is further object of the present invention to provide devices and methods for creating blood vessel grafts in vivo or in vitro.
These and other objects, features, and advantages of the present invention will become apparent upon review of the following detailed description of the invention taken in conjunction with the drawings and the appended claims.
Devices and methods are provided for forming a vascular graft by axially distending a blood vessel to stimulate vessel growth. Preferably, the device is implanted, for example using endoscopic techniques, for use in vivo. A portion of a blood vessel (i.e. the donor vessel) then is distended using the device. Preferred donor vessels include the gastroepipolic artery, as well as the internal mammary, femoral, splenic, and radial arteries. Then, the in vivo distended portion of the donor vessel is excised, for example, at the time of bypass surgery. In an alternative embodiment, a section of donor vessel is surgically excised from the bypass surgery patient and then distended in vitro in a medium for cell growth, e.g., in an organ culture system or bioreactor. Where the donor is the recipient of the graft, the result using either approach advantageously is a totally autologous, living vascular graft.
In a preferred embodiment, the device comprises a stretching mechanism which includes (i) a rigid body; (ii) a pair of posts comprising a first post and a second post which are connected to the body; (iii) a driver element slidably secured to the body and disposed between the pair of posts; and (iv) a means for sliding the driver element away from the pair of posts to axially distend a blood vessel positioned between the pair of posts and the driver element. The posts of the device preferably have a curved lateral surface having a radius of curvature large enough to avoid collapsing the blood vessel during stretching
In one variation, the body comprises a plate from which a pair of posts protrudes. This device may further include a second plate secured to the body defining a space in which the blood vessel is stretched. The posts can be integral with or attached to the base plate. In one embodiment, the posts are rotatably attached to the base plate.
In a more preferred, xe2x80x9cfoldable,xe2x80x9d variation, the body comprises a pair of movable arms connecting the pair of posts to the body. The arms can be oriented with the length of the body to provide a narrow device profile to facilitate in vivo insertion, and then once implanted can be deployed into a second position, suitable for blood vessel loading and stretching, approximately perpendicular to the longitudinal axis of the body. In this embodiment, the pair of moveable arms comprises a first arm and a second arm, each having a distal end and a proximal end, such that the proximal ends are hingedly connected to the body. The posts preferably are wheels rotatably attached to the distal end of each arm. Preferably, the body comprises a lower end portion that is adjustable to lock the moveable arms into two or more positions. The lower end portion can be biased by a spring to hold the lower end portion in engagement with the body.
The device typically includes a controller for controlling the means for sliding the driver element, in a continuous, intermittent, or cyclic manner. Preferably, the means for sliding the driver element comprises a prime mover that is mechanically, electromechanically, or hydraulically driven. In one embodiment, the device further comprises a guide rod, which passes through an aperture in the driver element to guide the movement of the driver element as the driver element is slid along the guide rod by the means for sliding. Other mechanisms for imparting lateral stability to the driver element include the use of a protrusion or groove that matingly engages with a corresponding groove in or protrusion from the body to guide the movement of the driver element as the driver element is slid by the means for sliding.
The means for sliding the driver element can include one or more springs. These springs can provide constant stretch or a nonlinear or a constant force-deformation response. In one embodiment, the spring can comprise a shape memory material so the spring""s stiffness or shape can be changed as stretching progresses or periodically.
The device optionally can include a growth factor or other growth stimulating agent for release in an effective amount to enhance growth of the blood vessel. Such agents may be impregnated into the materials of construction forming the device or can be in the form of a coating or a reservoir device attached to the stretching device.